Amyloid-beta (N3pE-40) ELISA kit

The pleiotropism of vitamin D is due to the presence of vitamin D receptor in the cells of nearly all tissues and organs within the human body. including the CNS. Multiple evidence is available to support neuroprotective properties of vitamin D. These include, for example, the presence of 25(OH)D-la-hydroxylase, an enzyme responsible for production of calcitriol, within the human brain. Among its other activities, calcitriol modifies production and release of neurotrophic factors, affects expression of genes associated with GABAergic signaling and stimulates biosynthesis of catecholamines. Antioxidative and anti-inflammatory properties were also demonstrated in research studies. By confronting the known pathomechanisms of Alzheimer's disease (AD) and the mechanism of action of vitamin D, one may propose that systemic insufficiency of vitamin D is a potential risk factor of AD. Studies conducted to date confirm the inverse relationship between serum calcidiol levels and the risk of dementia diseases, including AD. Elevated cerebrospinal fluid level of VDBP. a vitamin D binding protein that is also responsible for elimination of P-amyloid peptide (A(1), a pathogenic factor characteristic for AD, is considered to be a potential marker of AD. Reduction in AP levels within the CNS is the most important therapeutic target in the treatment of AD. Animal studies confirmed the impact of vitamin D-enriched diet on the reduction in tunyloid deposits, AP peptide levels and inflammatory reactions as well as on the increase in the level of neurotrophic factor within the brains of AP protein precursor (A beta PP)- transgenic mice. In case of AD, the purposefulness of initiating treatment before the onset of clinical symptoms is being highlighted. Vitamin D is worth consideration since by inducing the expression of VDR gene it leads, among others, to the silencing of the transcription of the gene encoding the A beta APP and thus inhibits its cleavage into peptides that form amyloid deposits. Despite the fact that at current state vitamin D can hardly be considered a therapeutic agent with an established efficient dose in AD, authors of studies suggest that it is important in AD prophylaxis in elderly patients with age-related reduction of serum calcidiol levels.

Nicastrin and its relative Nicalin (Nicastrin-like protein) are both members of larger protein complexes, namely gamma-secretase and the Nicalin-NOMO (Nodal modulator) complex. The gamma-secretase complex, which contains Presenilin, APH-1, and PEN-2 in addition to Nicastrin, catalyzes the proteolytic cleavage of the transmembrane domain of various proteins including the beta-amyloid precursor protein and Notch. Nicalin and its binding partner NOMO form a complex that was shown to modulate Nodal signaling in developing zebrafish embryos. Because its experimentally determined native size (200-220 kDa) could not be satisfyingly explained by the molecular masses of Nicalin (60 kDa) and NOMO(130 kDa), we searched in affinity-purified complex preparations for additional components in the low molecular mass range. A similar to 22-kDa protein was isolated and identified by mass spectrometry as transmembrane protein 147 (TMEM147), a novel, highly conserved membrane protein with a putative topology similar to APH-1. Like Nicalin and NOMO, it localizes to the endoplasmic reticulum and is expressed during early zebrafish development. Overexpression and knockdown experiments in cultured cells demonstrate a close relationship between the three proteins and suggest that they are components of the same complex. We present evidence that, similar to gamma-secretase, its assembly is hierarchical starting with the formation of a Nicalin-NOMO intermediate. Nicalin appears to represent the limiting factor regulating the assembly rate by stabilizing the other two components. We conclude that TMEM147 is a novel core component of the Nicalin-NOMO complex, further emphasizing its similarity with gamma-secretase.